Pain originating from the urinary bladder is a common clinical entity affecting more than 50% of females at some time in their lives. Some conditions are easy to treat, but others, such as interstitial cystitis (IC) have proven resistant to diagnosis and treatment. There are multiple proposed etiologies for IC with the common theme of an eventual sensitization/activation of sensory elements: abnormalities in the periphery lead to central neurophysiological changes that become expressed as enhanced sensory (pain-urgency) and reflex responses (i.e. reduced bladder capacity) which may outlast "triggering" events within the bladder. In somatic systems, it has been demonstrated that exposure to painful stimuli during early life can produce permanent changes in the neuroanatomical and neurophysiological substrates that process nociceptive information. Since 10-28% of adult patients with IC report urinary bladder symptoms as children a logical avenue for exploration is an examination of the effects of early-in-life painful bladder experiences on bladder responses in adults since individuals who are "primed" for hypersensitivity of the bladder could have pain that is both easily triggered and manifested as a sustained response to normally self-limited events. The hypothesis central to these studies is: A peripheral and spinal neuronal sensitization process initiated by early-in-life, high-intensity primary afferent activation, can enhance susceptibility to pathological urinary bladder pain as an adult. This early-in-life process leads to a hypersensitive state that is manifested by lowered intravesical stimulus thresholds needed for pain evocation and augmented responses to supra-threshold stimuli. To test this hypothesis reflex, primary afferent neuronal and spinal neuronal responses to urinary bladder distension (UBD) will be characterized in rats, which are given high-intensity UBD and/or inflammatory stimuli (intravesical zymosan) in the neonatal, pre-pubescent or post-pubescent periods. These exploratory studies will lay the groundwork for potential, novel therapeutic modalities for the treatment of urinary bladder pain by identifying substrates of hypersensitivity development and thereby treatment of urinary bladder pain by identifying substrates of hypersensitivity development and thereby presenting targets for intervention. Translation to the treatment of IC would be highly probable.